Characterization of Naïve and Vitamin C‑Treated Mouse Schwann Cell Line MSC80: Induction of the Antioxidative Thioredoxin Related Transmembrane Protein 1

Schwann cells (SCs) are essential in the production of the axon-wrapping myelin sheath and provide trophic function and repair mechanisms in the peripheral nerves. Consequently, well-characterized SC in vitro models are needed to perform preclinical studies including the investigation of the complex biochemical adaptations occurring in the peripheral nervous system (PNS) under different (patho)­physiological conditions. MSC80 cells represent a murine SC line used as an in vitro system for neuropathological studies. Here, we introduce the most abundant 9532 proteins identified via mass spectrometry-based protein analytics, and thus provide the most comprehensive SC protein catalogue published thus far. We cover proteins causative for inherited neuropathies and demonstrate that in addition to cytoplasmic, nuclear and mitochondrial proteins and others belonging to the protein processing machinery are very well covered. Moreover, we address the suitability of MSC80 to examine the molecular effect of a drug-treatment by analyzing the proteomic signature of Vitamin C-treated cells. Proteomic findings, immunocytochemistry, immunoblotting and functional experiments support the concept of a beneficial role of Vitamin C on oxidative stress and identified TMX1 as an oxidative stress protective factor, which might represent a promising avenue for therapeutic intervention of PNS-disorders with oxidative stress burden such as diabetic neuropathy.雪旺细胞（Schwann cells, SCs）是生成轴突包裹髓鞘的关键细胞，同时在周围神经中发挥营养支持与修复机制的作用。因此，构建经过充分表征的雪旺细胞体外模型，是开展临床前研究的必要前提，此类研究可用于探究不同病理生理条件下周围神经系统（peripheral nervous system, PNS）内发生的复杂生化适应性变化。MSC80细胞是一种小鼠雪旺细胞系，常被用作神经病理学研究的体外模型体系。本研究通过基于质谱的蛋白质组学分析，鉴定得到9532种高丰度蛋白质，由此构建了目前已发表的最为全面的雪旺细胞蛋白质组目录。该目录涵盖了与遗传性神经病致病相关的蛋白质，不仅覆盖了细胞质、细胞核与线粒体相关蛋白，还对蛋白质加工系统相关蛋白实现了良好的覆盖。此外，本研究通过分析维生素C处理细胞的蛋白质组特征，验证了MSC80细胞用于考察药物处理分子效应的适用性。蛋白质组学结果、免疫细胞化学实验、免疫印迹实验以及功能实验均证实，维生素C对氧化应激具有有益调控作用，并鉴定出TMX1作为氧化应激保护因子，这一发现或为治疗伴有氧化应激负担的周围神经系统疾病（如糖尿病性神经病）提供了极具潜力的干预靶点。